A tumor pH-responsive complex: Carboxyl-modified hyperbranched polyether and cis-dichlorodiammineplatinum(II)

To realize the pH-targeting delivery of antitumor drug cis-dichlorodiammineplatinum(II) (cisplatin, CDDP), a tumor pH-responsive polymer-platinum(II) complex (Suc-HPMHO–CDDP) from carboxyl-modified hyperbranched polyether (Suc-HPMHO) and cisplatin was designed and prepared. Because of the existence of hydrophobic core and ionization of surface carboxylic acid, Suc-HPMHO showed reversible pH-response in aqueous solution, and its responding pH value could be readily adjusted by only changing the degree of carboxylation of Suc-HPMHO. With plenty of terminal carboxyl groups, Suc-HPMHO could form the complex with CDDP by substituting the chloride ions with carboxyls. Methyl tetrazolium (MTT) assay showed that Suc-HPMHO had low cytotoxicity, while Suc-HPMHO–CDDP complex presented a similar antitumor effect with the free CDDP. Under the tumor acidic pH (pHe), Suc-HPMHO–CDDP complex deposited around/in cells because of its pH-response. Therefore, the pH-targeting of Suc-HPMHO–CDDP complex to tumor tissue could be realized. All of these results show that the tumor pH-responsive Suc-HPMHO–CDDP complex is a potential pH-targeting drug delivery system in cancer therapy.

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► Carboxyl-modified hyperbranched polyether was complexed with cisplatin.
► The complex showed pH-responsive behavior.
► The pH-targeting of complex to tumor tissue exhibited an efficient anticancer effect.